AB0611 Neutrophil extracellular traps and interstitial lung disease in ANCA-associated vasculitis: a scoping review
Authors: E. Conticini, M. D’alessandro, L. Bergantini, P. Falsetti, P. Cameli, E. Bargagli, L. Cantarini, B. Frediani
Journal: Annals of the Rheumatic Diseases (2022)

Background Deregulated neutrophil extracellular traps (NET) formation is implicated in various diseases, including ANCA-associated vasculitis and pulmonary fibrosis (PF). Lung involvement is frequent in AAV, and interstitial lung diseases (ILD) are strongly related to MPO-ANCA positivity and mainly reported in microscopic polyangiitis. The association between AAV and ILD is a strong indicator of poor prognosis and limited survival. Neutrophils, ANCA and NET interplay in PF development in AAV. Objectives This study aimed to review the literature concerning the implications of NET in lung fibrogenesis focused specifically on AAV associated with ILD, and the potential of NET as a theranostic marker. Methods Through scoping review methodology, we used a descriptive thematic analysis to understand the pathogenic role of NETs in patients with AAV and pulmonary fibrosis and their further role as a theranostic marker of this disease. Results Quality assessment of articles was evaluated through SANRA methodology (Table 1). The implications of NET in the pathogenesis of AAV and ILD (Figure 1), as well as an association between these two diseases, have been identified, but the underlying pathophysiological mechanisms are still unknown. Pharmacological or genetic inhibition of NET release reduces disease severity in multiple inflammatory disease models, indicating that NETs are potential therapeutic targets. In this regard, despite the lack of clinical data, we may hypothesize that an optimal management of AAV-ILD patients would require not only B-cells targeted therapy, but also NETs inhibition. Table 1. SANRA Score for quality assessment N°. Authors Justification of the article’s importance for the readership Statement of concrete aims or formulation of questions Description of the literature search Referencing Scientific Reasoning Appropriate presentation of data Total score 1 Pandolfi L et al. 2021 2 2 0 1 2 2 9 2 Radermecker C et al. 2020 1 2 0 2 2 1 8 3 Zhang S et al. 2019 2 1 0 2 2 1 8 4 Skopelja-Gardner S et al. 2019 1 1 0 1 2 2 7 5 Khawaja AA et al. 2020 2 2 0 1 2 1 8 6 Chrysanthopoulou A et al. 2014 2 1 0 2 2 1 8 7 Kraaij T et al. 2018 2 1 0 2 1 2 8 8 Tang S et al. 2015 2 1 0 1 2 1 7 9 Yoshida M et al. 2016 1 2 0 1 2 1 7 10 Nakazawa D et al. 2014 2 1 0 2 2 2 9 11 Hattanda F et al. 2019 2 2 0 1 2 1 8 12 Schreiber A et al. 2017 2 2 0 1 1 2 8 13 van Dam LS et al. 2019 2 2 0 1 1 1 7 14 Roitsch S et al. 2018 1 2 0 1 2 2 8 15 Takeuchi H et al. 2017 2 2 0 2 2 2 10 16 Su B et al. 2021 2 1 0 1 2 2 8 17 Söderberg D et al. 2015 2 1 0 1 2 1 7 18 Surmiak M et al. 2016 1 2 0 1 2 2 8 Figure 1. The role of NET in interstitial lung disease associated with ANCA-associated vasculitis Conclusion Preliminary findings seem to display a lack of efficacy of traditional immunosuppressants, such as Rituximab, in this subset of patients, while to date no patients suffering from a definite ILD was enrolled in clinical trials. Further insights would be provided by their employment, as a combination treatment, in the common clinical practice. Although we can imagine that inhibition of NETs in patients with AAV-ILD could reduce severity and mortality, we still lack a scientific basis that could improve our understanding of the disease from a molecular point of view. Disclosure of Interests None declared